The proposed project is directed toward the following goals: 1) Determination of the activity of two enzymes involved in the synthesis and degradation of folylpolyglutamates gamma-carboxypeptidase and folylpolyglutamate synthetase, in cultured cells of leukemia L1210 and several strains of sarcoma-180. 2) Correlation of activity of these enzymes with the forms of folylpolyglutamates in the cells. 3) Isolation and partial purification of these enzymes and study of their kinetics. 4) Synthesis of specific inhibitors of gamma-carboxypeptidase and folylpolyglutamate synthetase. 5) Study of the effect of these inhibitors on experimental animal tumors in rat and mouse. 6) Elucidation of the biological role of folylpolyglutamates as compared to that of monoglutamates. 7) Chemotherapeutic effect of 2,4-diamino-6-adamantyl-pteridine and its derivatives in animal tumors.